Impaired PIASy-Tip60 signaling weakens activation of p53 in melanoma

Alexander J. Lakhter, Sriramana Kanginakudru, Simon Warren, Christopher E. Touloukian, Raymond E. Boissy, Samisubbu R. Naidu

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

The tumor suppressor p53 plays a central role in preventing tumor development by promoting transcription of genes that stall cell cycle and induce cell death. Although the majority of melanomas express wild-type p53, the molecular mechanisms that impede its activation remain unclear. We previously reported that the SUMO E3 ligase PIASy and the histone acetyltransferase Tip60 signaling cascade promote p53-dependent autophagy and apoptosis. We hypothesized that impairment in this signaling attenuates p53, thus disabling its apoptotic function in melanoma. Here, we show that human melanoma patient samples and cell lines maintain p53 expression but PIASy and/or Tip60 are frequently lost. We observed dysregulation of Tip60-mediated p53 transcription program in melanoma cell lines. Reconstitution of PIASy and Tip60 in melanoma cells increased genotoxic stress-induced apoptosis. Our study provides a clinical link of how sumoylation signaling may activate p53-mediated cell death in melanoma.

Original languageEnglish (US)
Pages (from-to)213-217
Number of pages5
JournalMelanoma Research
Volume23
Issue number3
DOIs
StatePublished - Jun 1 2013

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Keywords

  • apoptosis
  • autophagy
  • melanoma
  • p53
  • PIASy
  • sumoylation
  • Tip60

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Dermatology

Cite this

Lakhter, A. J., Kanginakudru, S., Warren, S., Touloukian, C. E., Boissy, R. E., & Naidu, S. R. (2013). Impaired PIASy-Tip60 signaling weakens activation of p53 in melanoma. Melanoma Research, 23(3), 213-217. https://doi.org/10.1097/CMR.0b013e328361056d